FDA Approves Entyvio to Treat Ulcerative Colitis and Crohn's Disease

The U.S. Food and Drug Administration today approved Entyvio (vedolizumab) injection to treat adult patients with moderate to severe ulcerative colitis and adult patients with moderate to severe Crohn's disease.

Entyvio is approved to treat those conditions when one or more standard therapies (corticosteroids, immunomodulators, or tumor necrosis factor blocker medications) have not resulted in an adequate response.

Ulcerative colitis is a chronic disease that affects about 620,000 Americans. It causes inflammation and ulcers in the inner lining of the large intestine and is one of two main forms of chronic inflammatory bowel disease. The inflammation can lead to abdominal discomfort, gastrointestinal bleeding, and diarrhea.

Crohn's disease is a chronic inflammatory condition that causes inflammation, or swelling, and irritation of any part of the digestive tract—also called the gastrointestinal (GI) tract. More than a half million Americans have been diagnosed with Crohn's disease.

"Ulcerative colitis and Crohn's disease are debilitating diseases that impact the quality of life of those who have these conditions," said Amy G. Egan, M.D., M.P.H., acting deputy director of the Office of Drug Evaluation III in the FDA's Center for Drug Evaluation and Research. "Although there is no cure for these conditions, today's approval provides an important new treatment option for patients who have had an inadequate response to conventional therapy to help control their symptoms."

The safety and effectiveness of Entyvio for ulcerative colitis were established in two clinical trials involving approximately 900 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. Evaluations of patients included measures of stool frequency, rectal bleeding, endoscopic findings and a physician's overall assessment.

Results showed that a greater percentage of participants treated with Entyvio compared to a placebo achieved and maintained clinical response, achieved and maintained clinical remission, achieved corticosteroid-free clinical remission, and as seen during endoscopy, had improved appearance of the colon.

The safety and effectiveness of Entyvio for Crohn's disease were established in three clinical trials involving approximately 1,500 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. Results showed that a greater percentage of participants treated with Entyvio compared to a placebo achieved clinical response, achieved clinical remission, and achieved corticosteroid-free clinical remission.

Entyvio is an integrin receptor antagonist. Integrin receptors are proteins expressed on the surface of certain cells. Integrin receptors function as bridges for cell-cell interactions. Entyvio blocks the interaction of a specific integrin receptor (expressed on circulating inflammatory cells) with a specific protein (expressed on cells in the interior wall of blood vessels), and thereby blocks the migration of those circulating inflammatory cells across those blood vessels and into areas of inflammation in the gastrointestinal tract. The most common side effects in patients treated with Entyvio include headache, joint pain, nausea, and fever. The most serious risks associated with Entyvio include serious infections, hypersensitivity and infusion-related reactions; and hepatotoxicity.

Another type of integrin receptor antagonist has been associated with progressive multifocal leukoencephalopathy (PML), a rare and often fatal opportunistic infection of the central nervous system. PML is caused by a virus and typically only occurs in patients whose immune systems are compromised. There were no cases of PML identified among Entyvio clinical trial participants.

In Entyvio clinical trials, participants were actively monitored for PML with frequent and regular screenings, and evaluations of any new, unexplained neurological symptoms, as necessary. Because clinical trials are conducted under tightly controlled conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates that might be observed in practice. Therefore, while there were no cases of PML seen among patients participating in Entyvio clinical trials, there remains uncertainty regarding the risk of PML in patients taking Entyvio.

Health care professionals should monitor patients on Entyvio for any new onset, or worsening, of neurological signs and symptoms. The FDA will continue to work with the sponsor to further investigate the risk of PML through a required post-marketing study and enhanced, expedited adverse event reporting.

Consumers and health care professionals are encouraged to report adverse reactions from the use of Entyvio to the FDA's MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch (http://www.fda.gov/Safety/MedWatch/default.htm) or by calling 1-800-FDA-1088.